The present invention relates to drug delivery and pertains particularly to a method and apparatus for the transdermal delivery of drugs and other molecules.
The stratum corneum (SC) consists of a thin layer of dead cells with a high electrical resistance. This presents a major obstacle to the administration of drugs, immunizing agents, and genes transdermally. This layer can be perforated by the administration of short electrical field pulses, such as used in electroporation of cells. However, this perforation of the stratum corneum appears more appropriately referred to in terms of dielectric breakdown of the stratum corneum.
In my aforementioned applications, I disclose an apparatus and method for the electroporation of drugs, immunizing agents, and genes into surface cells, and a method and apparatus for the transdermal drug delivery by electrofusion of microbubbles to the tissue surface. In another application Ser. No. 07/907,322, entitled ELECTROPORATION METHOD AND APPARATUS FOR INSERTION OF DRUGS AND GENES INTO ENDOTHELIAL CELLS, filed Jul. 1, 1992, now U.S. Pat. No. 5,304,120 certain methods and apparatus are disclosed for insertion of drugs and genes into endothelial cells. The teachings of these are incorporated herein by reference.
In the second aforementioned parent application, I disclose methods and apparatus for the electroporation of drugs, immunizing agents, and genes into surface cells. In that application, apparatus is disclosed for delivery of a fluid medium carrying preselected molecules to a skin surface and thereafter applying electrical signals by means of electrodes to the surface tissue. The field is applied at a predetermined strength and duration in order to make the walls of the cells of the skin transiently permeable to permit the molecules to enter the preselected cells without damaging them.
One difficulty with the prior apparatus is that the stratum corneum (SC) which consists of a thin layer of dead cells with a high electrical resistance presents a major obstacle to the administration of drugs and genes transdermally. This layer can be perforated by the administration of short electrical field pulses, which creates a dielectric breakdown of the stratum corneum forming pores which can allow the passage of molecules.
Among the prior art relating generally to this field is the Weaver et al U.S. Pat. No. 5,019,034 entitled "Control of Transport of Molecules Across Tissue Using Electro-poration". Weaver seeks an alternative to the traditional syringe and gun injection of medications. He describes a proposal for using high voltage, short duration electrical pulses on the tissue surface to produce electroporation of the tissue to enable drugs and medication to pass into the tissue. However, he does not recognize or address the problem of the obstacle provided by the stratum corneum.
Another patent of interest is that of Grasso U.S. Pat. No. 4,955,378 entitled "Apparatus and Methods for Performing Electrofusion at Specific Anatomical Sites". He discloses a method of fusing biological particles to living tissue, preferably on corneas and in cervical areas. The tissue consists of living cells which are able to completely fuse with the biological particles, or live cells. Again, this does not address or solve the problem of transdermal transport of drugs, immunizing agents, and genes presented by the resistance of the stratum corneum. Also, neither of these patents provide or suggest any means to force the drugs, immunizing agents, or genes into or across the tissue surface.
The co-pending parent application presents an invention to overcome the problems of the prior art by providing means to overcome the resistance to the administration of drugs transdermally presented by the stratum corneum. In accordance with that invention, drugs, immunizing agents, or genes are loaded into microbubbles, the microbubbles are brought into physical contact with the tissue surface and a pulsed electrical field is applied between the microbubbles and the tissue by means of electrodes. This forms pores at the interface of the microbubbles and the tissue, such that the microbubbles fuse with the tissue and form a channel through which drugs and genes, which are under pressure from the microbubble to enter through the tissue. It is also applicable to the transport of drugs, immunizing agents, and genes across surfaces of other tissue such as membranes.
One problem with this approach is that it fails to provide sufficient control over the diffusion of drugs or the like in or into the tissue.
It is desirable that improved methods and apparatus be available for the transdermal delivery of drugs, immunizing agents, and genes.